Abstract Multistage enantioselective liquid–liquid extraction (ELLE) of 2‐phenylpropionic acid (2‐PPA) enantiomers using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as extractant was studied experimentally in a counter‐current cascade of centrifugal contactor separators (CCSs). Performance of the process was evaluated by purity (enantiomeric excess, ee ) and yield (Y). A multistage equilibrium model was established on the basis of single‐stage model for chiral extraction of 2‐PPA enantiomers and the law of mass conservation. A series of experiments on the extract phase/washing phase ratio (W/O ratio), extractant concentration, the pH value of aqueous phase, and the number of stages was conducted to verify the multistage equilibrium model. It was found that model predictions were in good agreement with the experimental results. The model was applied to predict and optimize the symmetrical separation of 2‐PPA enantiomers. The optimal conditions for symmetric separation involves a W/O ratio of 0.6, pH of 2.5, and HP‐β‐CD concentration of 0.1 mol L −1 at a temperature of 278 K, where ee eq (equal enantiomeric excess) can reach up to 37% and Y eq (equal yield) to 69%. By simulation and optimization, the minimum number of stages was evaluated at 98 and 106 for ee eq > 95% and ee eq > 97%. Chirality 28:235–244, 2016 . © 2016 Wiley Periodicals, Inc. Research highlights are as follows: Multistage enantioselective liquid‐liquid extraction is suitable for the separation of 2‐phenylpropionic acid enantiomers with HP‐β‐CD as hydrophilic chiral selector. Model predictions of multistage countercurrent centrifugal extraction of 2‐phenylpropionic acid enantiomers are in good agreement with the experimental results. Purity for 2‐phenylpropionic acid enantiomers could be remarkably improved by changing W/O ratio or extractant concentration, and or adding the number of centrifugal contact separators. Multistage enantioselective liquid‐liquid extraction in centrifugal contactor separators can be hopeful for separations of various enantiomers at a large‐scale.
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